This study was conducted to compare the effect of supplementing yeast combined with chromium methionine (Cr-Met) or niacin or their mixture into rations of lactating buffaloes on their productive performance over 120 days of an experimental period under summer season conditions. Twelve lactating buffalos with an average 550 Kg live body weight and in their 4th or 5th seasons at mid-lactation, were divided randomly into four similar groups (three buffaloes per group) according to their live body weight and milk yield. Dietary treatments (on DM) were as follows: (T1) control ration that free from feed additives, T2: control ration plus 10g yeast + 5g Cr-Met, T3: control ration plus 10g yeast + 5g niacin and T4: control ration plus 10g yeast + 5g Cr-Met + 5g niacin. The experimental rations were formulated to cover maintenance and production allowance according to Kearl (1982) for dairy cattle. Results indicated that supplementing lactating buffalo rations with different feed additives (T2, T3 and T4) improved the digestibility of most nutrients and feeding values as TDN and DCP than those of control one (T1). No significant differences were found respecting most blood serum constituents among all groups of lactating buffaloes, except globulin concentration was significantly (P<0.05) lower with those fed tested rations compared with that of control group. The 7% - FCM yield was significantly (P<0.05) higher for all tested rations (T2, T3 and T4) than that of control one (T1). Also, 7% - FCM yield of both tested rations (T3 and T4) was significantly (P<0.05) higher than that in tested one (T2), being the highest value was recorded with T4 ration that supplemented with the mixture of additives (yeast - Cr-Met - niacin). The daily 7% - FCM yield was increased by (11.18%) for T2, (15.91%) for T3 and (18.43%) for T4 supplemented rations compared with unsupplemented ration (T1). Milk composition was not affected by any treatments except lactose percentage which was significantly (P<0.05) decreased with those fed T2 – ration compared with those fed other experimental rations (T1, T3 and T4). Likewise, feed conversion was significantly (P<0.05) improved with all animals fed tested rations (containing feed additives) being the best improvement was occurred with mixture of supplements (yeast plus Cr-Met and niacin). Meanwhile, relative economic efficiency was 5.3, 6.5 and 7.8 % for tested rations T2, T3 and T4, respectively being better than that of control one (T1). Generally, from the obtained results indicated that the supplementation of different feed additives to lactating buffalo rations had positive effects on digestibility, feeding value, some blood serum parameter, milk yield and economic efficiency.